{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:03:03Z","timestamp":1787022183103,"version":"build-2736575974"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>The demand for transplant organs far exceeds the available supply. In the United States alone, more than 90,000 patients are currently on the kidney transplant waitlist, yet only about one third of them will ever receive a transplant. Xenotransplantation, organ transplants from gene edited pigs, offers a potential solution to this shortage. Successful investigational transplants of pig kidneys into brain-dead recipients and expanded access cases involving living human recipients have resulted in the green-lighting of the first human clinical trials. Using the benchmark of 2-year survival of non-human primates in pre-clinical studies, we developed a tool that can identify individual wait-listed patients predicted to have a shorter life expectancy than with a xenotransplant, utilizing Random Survival Forest, DeepSurv and Cox Proportional-Hazards models. We found that it is hard to identify patients that reach clinical equipoise unless the expected xenograft survival exceeds two years, with the Random Survival Forest model identifying less than 5% of such patients. Few patients would benefit based on survival alone and potential beneficiaries are spread across more than 200 transplant centers. Several incentives could allow more patients to reach equipoise. At the same benchmark of 2-year xenograft survival, keeping patients inactive on the waitlist while they have a functioning xeno-kidney increases the percentage achieving equipoise by up to 1.7% across cohorts. Granting patients with failed xenografts the same priority as prior living donors increases this by up to 17.9%, while assigning them the highest priority raises it by up to 28.5%. We are able, however, to identify phenotypes that have a high mortality and low transplant rates in the current allocation system that could serve as acceptable candidates; while not achieving equipoise, they would enjoy the benefits of being dialysis free.<\/jats:p>","DOI":"10.1371\/journal.pone.0335767","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T18:55:42Z","timestamp":1764615342000},"page":"e0335767","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["A data-driven analysis of patient selection for xenotransplant human clinical trials"],"prefix":"10.1371","volume":"20","author":[{"given":"Baris","family":"Ata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Montgomery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2619-655X","authenticated-orcid":true,"given":"Yucel Naz","family":"Ozyoruk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan","family":"Parent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse D.","family":"Schold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"pone.0335767.ref001","unstructured":"Organ Procurement and Transplantation Network. Organ Procurement and Transplantation Network National Data; 2025. https:\/\/optn.transplant.hrsa.gov\/data\/view-data-reports\/national-data\/"},{"issue":"41","key":"pone.0335767.ref002","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.aau6298","article-title":"Transplanting organs from pigs to humans","volume":"4","author":"M Sykes","year":"2019","journal-title":"Sci Immunol."},{"issue":"5","key":"pone.0335767.ref003","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1111\/tri.13104","article-title":"Xenotransplantation: back to the future?","volume":"31","author":"RPH Meier","year":"2018","journal-title":"Transpl Int."},{"issue":"9","key":"pone.0335767.ref004","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1097\/TP.0000000000003632","article-title":"Suggested patient selection criteria for initial clinical trials of pig kidney xenotransplantation in the United States","volume":"105","author":"A Jagdale","year":"2021","journal-title":"Transplantation."},{"issue":"20","key":"pone.0335767.ref005","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1056\/NEJMoa2120238","article-title":"Results of two cases of pig-to-human kidney xenotransplantation","volume":"386","author":"RA Montgomery","year":"2022","journal-title":"N Engl J Med."},{"key":"pone.0335767.ref006","unstructured":"The New York Times. In a first, surgeons attached a pig kidney to a human, and it worked. The New York Times. 2021."},{"issue":"4","key":"pone.0335767.ref007","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1111\/ajt.16930","article-title":"First clinical-grade porcine kidney xenotransplant using a human decedent model","volume":"22","author":"PM Porrett","year":"2022","journal-title":"Am J Transplant."},{"key":"pone.0335767.ref008","unstructured":"Langone Health N. Two-month study of pig kidney xenotransplantation gives new hope for future organ supply. 2023. https:\/\/nyulangone.org\/news\/two-month-study-pig-kidney-xenotransplantation-gives-new-hope-for-future-organ-supply"},{"key":"pone.0335767.ref009","unstructured":"Massachusetts General Hospital. World\u2019s first genetically edited pig kidney transplant into living recipient. 2024. https:\/\/www.massgeneral.org\/news\/press-release\/worlds-first-genetically-edited-pig-kidney-transplant-into-living-recipient"},{"key":"pone.0335767.ref010","unstructured":"Langone Health N. First-ever combined heart pump & gene-edited pig kidney transplant gives new hope to patient with terminal illness. 2024. https:\/\/nyulangone.org\/news\/first-ever-combined-heart-pump-gene-edited-pig-kidney-transplant-gives-new-hope-patient-terminal-illness"},{"issue":"1","key":"pone.0335767.ref011","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1056\/NEJMoa2201422","article-title":"Genetically Modified Porcine-to-Human Cardiac Xenotransplantation","volume":"387","author":"BP Griffith","year":"2022","journal-title":"N Engl J Med."},{"key":"pone.0335767.ref012","unstructured":"University of Maryland Medical Center. UM Medicine Faculty-Scientists and Clinicians Perform Second Historic Transplant of Pig Heart into Patient with End-Stage Cardiovascular Disease; 2023. https:\/\/www.medschool.umaryland.edu\/news\/2023\/um-medicine-faculty-scientists-and-clinicians-perform-second-historic-transplant-of-pig-heart-into-patient-with-end-stage-cardiovascular-disease.html"},{"issue":"19","key":"pone.0335767.ref013","doi-asserted-by":"crossref","DOI":"10.1172\/JCI164484","article-title":"A roadmap for human trials of xenotransplantation","volume":"132","author":"PM Porrett","year":"2022","journal-title":"J Clin Invest."},{"key":"pone.0335767.ref014","doi-asserted-by":"crossref","first-page":"900594","DOI":"10.3389\/fimmu.2022.900594","article-title":"Xenotransplantation: A New Era","volume":"13","author":"AN Carrier","year":"2022","journal-title":"Front Immunol."},{"issue":"10","key":"pone.0335767.ref015","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1111\/ajt.15916","article-title":"Pig-to-human heart transplantation: who goes first?","volume":"20","author":"3rd Pierson RN","year":"2020","journal-title":"Am J Transplant."},{"issue":"3","key":"pone.0335767.ref016","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.kint.2022.05.025","article-title":"A tool for decision-making in kidney transplant candidates with poor prognosis to receive deceased donor transplantation in the United States","volume":"102","author":"JD Schold","year":"2022","journal-title":"Kidney Int."},{"issue":"5","key":"pone.0335767.ref017","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1287\/mnsc.42.5.629","article-title":"Involving patients in the cadaveric kidney transplant allocation process: a decision-theoretic perspective","volume":"42","author":"J-H Ahn","year":"1996","journal-title":"Management Science."},{"key":"pone.0335767.ref018","doi-asserted-by":"crossref","unstructured":"Ata B, Friedewald JJ, Randa AC. Organ transplantation. Handbook of healthcare analytics: Theoretical minimum for conducting 21st century research on healthcare operations. 2018. p. 187\u2013215.","DOI":"10.1002\/9781119300977.ch9"},{"issue":"5","key":"pone.0335767.ref019","doi-asserted-by":"crossref","first-page":"768","DOI":"10.3390\/healthcare11050768","article-title":"Operations research to solve kidney allocation problems: a systematic review","volume":"11","author":"N Sekercioglu","year":"2023","journal-title":"Healthcare (Basel)."},{"key":"pone.0335767.ref020","unstructured":"Ahn JH. Optimal option-exercising strategy with an application for kidney transplant decisions. Stanford University; 1994."},{"issue":"9","key":"pone.0335767.ref021","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1016\/j.ajt.2023.05.010","article-title":"American Society of Transplant Surgeons-American Society of Transplantation report of FDA meeting on regulatory expectations for xenotransplantation products","volume":"23","author":"A Adams","year":"2023","journal-title":"Am J Transplant."},{"issue":"6","key":"pone.0335767.ref022","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.ajt.2024.03.015","article-title":"Research opportunities and ethical considerations for heart and lung xenotransplantation research: a report from the National Heart, Lung, and Blood Institute workshop","volume":"24","author":"KK Khush","year":"2024","journal-title":"Am J Transplant."},{"issue":"3","key":"pone.0335767.ref023","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1017\/S096318012300052X","article-title":"Xenotransplantation clinical trials and equitable patient selection","volume":"33","author":"C Bobier","year":"2024","journal-title":"Camb Q Healthc Ethics."},{"issue":"9","key":"pone.0335767.ref024","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1097\/TP.0000000000005384","article-title":"Patient selection for xenotransplant human clinical trials: a data-driven approach","volume":"109","author":"B Ata","year":"2025","journal-title":"Transplantation."},{"key":"pone.0335767.ref025","unstructured":"U S Renal Data System. 2023 USRDS Annual Data Report: Epidemiology of Kidney Disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2023."},{"issue":"3","key":"pone.0335767.ref026","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1214\/08-AOAS169","article-title":"Random survival forests","volume":"2","author":"H Ishwaran","year":"2008","journal-title":"The annals of applied statistics."},{"issue":"1","key":"pone.0335767.ref027","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s12874-018-0482-1","article-title":"DeepSurv: personalized treatment recommender system using a Cox proportional hazards deep neural network","volume":"18","author":"JL Katzman","year":"2018","journal-title":"BMC Med Res Methodol."},{"issue":"2","key":"pone.0335767.ref028","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.2517-6161.1972.tb00899.x","article-title":"Regression models and life-tables","volume":"34","author":"DR Cox","year":"1972","journal-title":"Journal of the Royal Statistical Society Series B: Statistical Methodology."},{"issue":"8","key":"pone.0335767.ref029","article-title":"Cellular dynamics in pig-to-human kidney xenotransplantation","volume":"5","author":"W Pan","year":"2024","journal-title":"Med."},{"issue":"5","key":"pone.0335767.ref030","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1038\/s41591-024-02972-1","article-title":"Integrative multi-omics profiling in human decedents receiving pig heart xenografts","volume":"30","author":"E Schmauch","year":"2024","journal-title":"Nat Med."},{"issue":"10408","key":"pone.0335767.ref031","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/S0140-6736(23)01349-1","article-title":"Immune response after pig-to-human kidney xenotransplantation: a multimodal phenotyping study","volume":"402","author":"A Loupy","year":"2023","journal-title":"Lancet."},{"issue":"8","key":"pone.0335767.ref032","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1038\/s41591-023-02471-9","article-title":"Pig-to-human heart xenotransplantation in two recently deceased human recipients","volume":"29","author":"N Moazami","year":"2023","journal-title":"Nat Med."},{"issue":"22","key":"pone.0335767.ref033","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1056\/NEJM199105303242208","article-title":"Of mice but not men. Problems of the randomized clinical trial","volume":"324","author":"S Hellman","year":"1991","journal-title":"N Engl J Med."},{"issue":"3","key":"pone.0335767.ref034","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1056\/NEJM198707163170304","article-title":"Equipoise and the ethics of clinical research","volume":"317","author":"B Freedman","year":"1987","journal-title":"N Engl J Med."},{"issue":"2","key":"pone.0335767.ref035","doi-asserted-by":"crossref","first-page":"4","DOI":"10.2307\/3564143","article-title":"Commentary: the randomized clinical trial: for whose benefit?","volume":"7","author":"A Schafer","year":"1985","journal-title":"IRB: Ethics & Human Research."},{"key":"pone.0335767.ref036","first-page":"1","article-title":"Guideline on infectious disease issues in xenotransplantation","volume":"50","year":"2001","journal-title":"MMWR Recommendations and Reports."},{"issue":"5","key":"pone.0335767.ref037","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/hast.1419","article-title":"Reevaluating the ethical issues in porcine-to-human heart xenotransplantation","volume":"52","author":"H Silverman","year":"2022","journal-title":"Hastings Cent Rep."},{"issue":"9","key":"pone.0335767.ref038","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/j.healun.2022.06.008","article-title":"Ethics and the emerging use of pig organs for xenotransplantation","volume":"41","author":"A Caplan","year":"2022","journal-title":"J Heart Lung Transplant."},{"issue":"1","key":"pone.0335767.ref039","article-title":"Transplant patients\u2019 perceptions about participating in first-in-human pig kidney xenotransplant clinical trials: a mixed methods study","volume":"32","author":"EJ Gordon","year":"2025","journal-title":"Xenotransplantation."},{"issue":"9","key":"pone.0335767.ref040","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1097\/TP.0000000000004144","article-title":"Informed consent for potential recipients of pig kidney xenotransplantation in the United States","volume":"106","author":"LA Padilla","year":"2022","journal-title":"Transplantation."},{"issue":"4","key":"pone.0335767.ref041","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1111\/bioe.13262","article-title":"Xenograft recipients and the right to withdraw from a clinical trial","volume":"38","author":"C Bobier","year":"2024","journal-title":"Bioethics."},{"issue":"3","key":"pone.0335767.ref042","doi-asserted-by":"crossref","DOI":"10.1111\/xen.70052","article-title":"Ethical analysis of voluntariness in pig kidney xenotransplant first-in-human clinical trials","volume":"32","author":"ML Houston","year":"2025","journal-title":"Xenotransplantation."},{"key":"pone.0335767.ref043","unstructured":"OPTN\/UNOS Ethics Committee. White Paper: Manipulation of the Organ Allocation System Waitlist Priority through the Escalation of Medical Therapies. Organ Procurement and Transplantation Network \/ United Network for Organ Sharing; 2018. https:\/\/optn.transplant.hrsa.gov\/professionals\/by-topic\/ethical-considerations\/"},{"issue":"1","key":"pone.0335767.ref044","first-page":"61","article-title":"Paying research participants: regulatory uncertainty, conceptual confusion, and a path forward","volume":"17","author":"EA Largent","year":"2017","journal-title":"Yale J Health Policy Law Ethics."},{"issue":"9","key":"pone.0335767.ref045","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1136\/jme-2023-109298","article-title":"Update on the ethical, legal and technical challenges of translating xenotransplantation","volume":"50","author":"R Thom","year":"2024","journal-title":"J Med Ethics."},{"key":"pone.0335767.ref046","unstructured":"Kahn JP, Mastroianni AC, Sugarman J. Beyond consent: seeking justice in research. Oxford: Oxford University Press; 2018."}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0335767","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T18:55:49Z","timestamp":1764615349000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0335767"}},"subtitle":[],"editor":[{"given":"Chen","family":"Ling","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,12,1]]},"references-count":46,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0335767","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,1]]}}}